Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of a proprietary matrix metalloproteinase (MMP) inhibitor, AQU-118, for blocking mechanical allodynia and bone & nerve compression pain in a rodent model of bone cancer. The goals for Phase I are to scale-up the synthesis of AQU-118, determine its oral pharmacokinetics (PK) and target tissue penetration, and determine its efficacy in a mouse bone cancer pain model via NCTC 2472 fibrosarcoma cell implantation. The primary read-outs will be measuring mechanical allodynia and motion induced pain. The secondary read- out will be to measure the extent of bone density loss and tumor growth. A follow-up biomarker and gelatin zymography analysis will be performed to determine if any behavioral changes observed from the animal model as a result of dosing with AQU-118 correspond to changes in metalloproteinase (MMP-2, MMP-9), cytokine (IL-1 , IL-6) & EphB1/EphrinB1 levels in serum and/or target tissue. The ultimate goal of the proposed work is to evaluate whether a matrix metalloproteinase inhibitor can be used to significantly reduce bone cancer pain and bone density loss without the side-effects of euphoria, tolerance and addiction.